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Sökning: WFRF:(Bronson R)

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  • Botvinik-Nezer, Rotem, et al. (författare)
  • Variability in the analysis of a single neuroimaging dataset by many teams
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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  • Bronson, P. G., et al. (författare)
  • Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency
  • 2016
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 48:11, s. 1425-1429
  • Tidskriftsartikel (refereegranskat)abstract
    • Selective immunoglobulin A deficiency (IgAD) is the most common p rimary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 x 10(-8)) loci and association with a rare IFIH1 variant (p.11e923Val). Peak new variants (PVT1, P = 4.3 x 10(-11); ATG13-AMBRA1, P = 6.7 x 10(-10); AHI1, P = 8.4 x 10(-10); CLEC16A, P = 1.4 x 10(-9)) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3(+) regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P <= 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD.
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  • Albertsson, Anna-Maj, et al. (författare)
  • γδ T cells contribute to injury in the developing brain.
  • 2018
  • Ingår i: The American journal of pathology. - 1525-2191. ; 188:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurological disabilities. Inflammation contributes to the development of perinatal brain injury, but the essential mediators leading to brain injury in early life remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However γδT-cells are already functionally competent during early development and are important in early life immunity. We investigated the potential contribution of γδT-cells to preterm brain injury by using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury-the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT-cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT-cells provided protection in the mouse model. The common γδT-cell associated cytokines interferon-γ and interleukin (IL)-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain where, unlike injury in the mature brain, γδT-cells function as important initiators of injury independently of common γδT-cell associated cytokines. This new finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.
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